“Pay-to-participate” stem cells studies: an interview with Leigh Turner
In this interview, Leigh Turner, Associate Professor, University of Minnesota Center for Bioethics, School of Public Health and College of Pharmacy, discusses his recent paper, published in Regenerative Medicine, on “pay-to-participate” stem cells studies.
In this interview, Leigh Turner, Associate Professor, University of Minnesota Center for Bioethics, School of Public Health and College of Pharmacy, discusses his recent paper, published in Regenerative Medicine, on “pay-to-participate” stem cells studies and the role of ClinicalTrials.gov.
You just published in Regenerative Medicine an article about “pay-to-participate” stem cells studies that are registered and listed on the U.S. National Institutes of Health website, ClinicalTrials.gov. What prompted you to write this paper?
One of my current areas of research involves studying U.S. businesses that engage in direct-to-consumer marketing of putative stem cell treatments. I use empirical research methods to investigate where such businesses are located, what kinds of diseases and injuries they claim to treat, what kinds of stem cells they purport to use and what marketing techniques they use in an attempt to confer legitimacy on their commercial practices. I’m equally interested in the many ethical, social and regulatory issues generated by such businesses. Many of these businesses use websites, social media, YouTube videos, webinars and other tools to engage in direct-to-consumer marketing of supposed stem cell therapies. To my surprise, at one point I noticed that some of these companies had successfully listed “pay-to-participate” studies on ClinicalTrials.gov. Many of these “studies” look to me like little more than marketing exercises, though of course the businesses listing them would presumably argue that they are genuine clinical studies.
I’m going to have some critical remarks to make about ClinicalTrials.gov and the failure of NIH officials to require better screening of studies submitted to ClinicalTrials.gov. Before I offer those critiques let me emphasize what a terrific public resource ClinicalTrials.gov is. I use it as a researcher and, like many others, I have used the database to search for clinical studies that might be suitable for a family member. I care about ClinicalTrials.gov and I regard it as a collective good that needs to be protected from parties willing to misuse and abuse it. That’s the problem with collective goods based on the honor system. Not everyone plays by those rules.
You went from noticing a few of these study listings to taking a more systematic approach to the topic. Tell us what you found.
Businesses that engage in direct-to-consumer promotion of what they proclaim are stem cell therapies while also claiming to study those very “treatments” in the context of “clinical studies” can be sorted into at least three distinct categories.
In one category are companies that list on ClinicalTrials.gov what they call “patient-funded”, “patient-sponsored” or “self-funded” studies. Phrases in the study listings reveal that individuals are charged to participate in these studies. I found two such businesses; one company has registered five pay-to-participate stem cells studies and the other one has listed two such studies. The number has actually increased since I completed my analysis. I focused on U.S. based businesses and studies with U.S. clinical sites. The company with five pay-to-participate studies tied to a clinic in Florida had also listed more of these pay-to-participate studies with clinical sites in Mexico. I hadn’t counted those studies because I was focusing on the U.S. aspect of this phenomenon. Two of those studies are now listed as taking place at the Florida clinic rather than at the facility in Tijuana. And so, the list of studies in Table One of my article could be expanded since there are now two more “patient-sponsored” stem cell studies apparently taking place within the U.S. In those studies, individuals with, respectively, Parkinson’s disease and multiple sclerosis are charged to participate in studies within which they are administered autologous adipose-derived stem cells.
In a second category are businesses that don’t disclose in their ClinicalTrials.gov listings that individuals must pay to enroll in these studies. Elsewhere, however, these businesses acknowledge that individuals pay to participate in their studies. I found eleven such studies. They had been registered by a total of five businesses. These listings weren’t as easy to find as the studies in Table One of my article because it was necessary to connect the ClinicalTrials.gov listings to claims made elsewhere that individuals are in fact charged to be in these studies. It took some effort to connect the dots. I suspect my article undercounts the number of businesses that have registered such studies and the total number of such pay-to-participate studies. There are some companies that I believe belong on this list but I had reservations about the quality and volume of publicly available information that could be used to build the case for their inclusion. That takes me to the third category of businesses and studies.
The businesses in this third category aren’t mentioned by name in my paper and I don’t identify and describe the studies they have listed on ClinicalTrials.gov. It appears that some U.S. businesses are listing pay-to-participate studies on ClinicalTrials.gov while also being unforthcoming about what they are doing. Some of these companies seem to make active attempts to conceal that they charge individuals to participate in clinical studies. I have a pretty good idea of what some of these companies are doing and I wish I could have described their studies in my article. I allude to the existence of such businesses but they aren’t named and their studies aren’t identified. You can guess why. Had I described these businesses there would be at least ten more pay-to-participate studies listed in my article.
I should add that the tallies for businesses and studies would also be far higher had I included the many pay-to-participate studies registered by international “stem cell clinics.” I was interested in using U.S. federal regulations as a tool for evaluating the commercial practices of U.S. businesses but there are plenty of international companies that have registered such studies on ClinicalTrials.gov. Do officials at the NIH have any idea how many of these studies are in their database? I wonder.
In your article, you express various concerns about “pay-to-participate stem cell studies.” Why do you find such studies problematic?
The vast majority of the U.S. businesses that engage in direct-to-consumer marketing of purported stem cell treatments argue that the cells they administer to their clients are not subject to FDA oversight. They make the same claims about the pay-to-participate studies they have registered on ClinicalTrials.Gov. They claim institutional review board (IRB) review is sufficient–it’s actually not clear whether all of the studies I review in my paper have been approved by IRBs–and they argue that they are under no obligation to submit their studies to the FDA. In my paper, I argue that many of these studies appear to require Investigational New Drug (IND) applications that have been submitted to the FDA and cleared by the Center for Biologics Evaluation and Research. I also note that when INDs are required, businesses aren’t free to charge study participants whatever they please. Rather, according to federal regulations, if organizations conducting studies done under INDs want to engage in cost-recovery – which is not the same as trying to profit by claiming to offer “stem cell treatments” in the context of “stem cell studies” – they need to prepare a detailed rationale and a budget, and obtain approval from the FDA. There are at least two ways in which many pay-to-participate stem cell studies appear to operate outside the federal regulatory framework that specifies how clinical studies are supposed to be conducted. But I’ve focused on regulatory issues in this response to your question when my concerns go well beyond matters of regulatory compliance and noncompliance.
If you take a careful look at many of these pay-to-participate studies you find what in numerous cases appear to be studies with serious scientific and ethical shortcomings. In some instances, there is no record of peer-reviewed preclinical studies being done before stem cells are administered – for thousands or tens of thousands of dollars – to humans. Have some businesses done no preclinical research before registering studies on ClinicalTrials.gov and charging individuals to participate in their studies? I suppose a counterargument is that perhaps some businesses have done such research but it cannot be found in the peer-reviewed literature. Still, I am concerned that some businesses seem to be entering the direct-to-consumer marketplace–whether using the language of “treatments” or “innovative studies,” or blurring such distinctions–without doing meaningful pre-clinical research. If this is happening patients are exposed to an unnecessary and avoidable level of risk when they pay to participate in such studies.
There is then a widespread failure to use randomization, blinding and either placebos or sham surgical procedures, where the latter can be ethically and scientifically justified. In cases, where effective treatments exist and there is a standard of care that could be used as a point of comparison against investigational stem cell interventions, it is atypical to find stem cell interventions for which study subjects are charged tested against the current standard of care. To date I haven’t found such a pay-to-participate stem cell study.
There are numerous well-known steps that can be taken to deal with various kinds of biases but pay-to-participate studies are usually open-label, without controls and non-randomized. Of course, there is also the observer bias that can occur when the doctor running the study is being paid per stem cell infusion or injection. The failure to blind and randomize study subjects can also inform the experiences of individuals who have paid thousands or tens of thousands of dollars to undergo what has been marketed to them as a promising stem cell treatment or innovative stem cell therapy.
Many of these studies are bad science and some of them are so poorly designed that in reality they are nothing more than junk science. There are, of course, variations in the ethical and scientific problems associated with such studies. In some cases, the chief problem might be an unqualified or underqualified PI. In other studies, the most salient problem is the lumping together into the same study individuals with very different medical conditions. Do we really want individuals with Alzheimer’s disease, ALS, multiple sclerosis, Parkinson’s disease, cardiomyopathy, degenerative hip disease, spinal cord injuries or erectile dysfunction all in the same study? In what world of clinical research does that jumbling together of individuals and diseases make sense? How can you possibly get meaningful data from such studies?
It is striking how many pay-to-participate studies involve administration of autologous adipose-derived or bone marrow derived “stem cells” for a bizarre array of diseases and injuries. This is what happens when stem cells are not tested as biological products within carefully designed and conducted clinical studies restricted to well-defined populations of research subjects and instead are misrepresented as panaceas.
What do you hope publication of your article will accomplish?
The NIH needs to better screen studies submitted to ClinicalTrials.gov. Other clinical trial registries need to do likewise. I focus on pay-to-participate stem cell studies listed in ClinicalTrials.gov but such studies can be found in other registries.
ClinicalTrials.gov now has a disclaimer that states: “Listing of a study on this site does not reflect endorsement by the National Institutes of Health (NIH).” That disclaimer simply isn’t sufficient. Patients and their loved ones, physicians, researchers, journalists, and many other individuals all use ClinicalTrials.gov because they regard the registry and database as a source of meaningful, credible information about clinical studies. I suspect most individuals would be shocked at how easy it is to register on ClinicalTrials.gov studies that have obvious methodological problems, do not appear to comply with applicable federal regulations or have glaring ethical shortcomings. ClinicalTrials.gov needs to raise the bar and perform a proper review of studies before they are registered. As I press this point let me emphasize that I know careful screening by NIH officials will require more resources and I am making this argument at a time when much of the political discourse in the U.S. is about cutting funding for the CDC, FDA, NIH and other federal agencies.
Patients have already been injured as a result of going to ClinicalTrials.gov, thinking they had found a legitimate clinical study, and then suffering harm after undergoing unproven and unlicensed stem cell interventions. There are going to be more reports of individuals who suffer injuries or allege that they have been defrauded if studies aren’t better screened. There will be “collateral damage” if the status quo persists. It’s easy to imagine what will happen. Individuals with ALS, MS, Parkinson’s disease or any of dozens of other diseases or injuries will find a “study” on ClinicalTrials.gov, pay to enroll in a study or be told they’re getting a promising stem cell treatment and they’ll end up being injured by an intervention that isn’t evidence-based and poses unnecessary risk of harm.
At root, the marketplace of businesses selling unlicensed and unproven stem cell interventions needs to be addressed and better regulated. Even so, better screening of studies listed in ClinicalTrials.gov would at least have the effect of not allowing businesses to take advantage of the legitimacy and credibility that many individuals attribute to ClinicalTrials.gov and the studies listed in it.
Do you think your article will have an impact? Are policy-makers and NIH officials likely to share your concerns?
Some good investigative reporting would be a great start. People need to know there is a real problem with ClinicalTrials.gov, even though it remains a valuable public resource and a collective good worthy of public funding. I’m hoping my article will provide journalists with some tools and starting points they can use to further dig into the world of pay-to-participate stem cell studies listed on ClinicalTrials.gov as well as the businesses that registered them. Perhaps such coverage will help convince NIH officials that they have a crucial role to play in making ClinicalTrials.gov a resource people can turn to for informative about credible clinical trials rather than allowing it to become a database corrupted and devalued by highly problematic studies. There is a role for the FDA as well if I’m right and there are pay-to-participate studies being conducted without cleared IND applications even though INDs are needed for at least some of these studies.
“We need more sunshine” is something you often hear about questionable commercial activities but in the U.S. it is astonishing what business practices are permitted to occur in broad daylight, visible to anyone who cares to pay attention. Part of the problem is the routine devaluation of regulatory agencies. You need investigators to inspect questionable commercial practices and clinical activities but where are the regulators in an era of hiring freezes, job cuts and budget cuts? Even so, perhaps there are ways to jolt into action people who are in positions of power and who can act to help prevent the spread of misinformation, bad science, and marketing packaged as clinical research.
Turner, L. ClinicalTrials.gov, stem cells and pay-to-participate clinical studies. Regen. Med. doi: 10.2217/rme-2017-0015 (2017) (Epub ahead of print)
The opinions expressed in this interview are those of the interviewee and do not necessarily reflect the views of Future Medicine Ltd.